Cushing's syndrome

Question 1

What is cushing’s syndrome and cushing’s disease?

Answer 1

Cushing’s syndrome refers to the signs and symptoms that develop following prolonged elevation of cortisol

Cushing’s disease refers to the condition where a pituitary adenoma (tumour) secretes excessive ACTH leading to adrenal hyperplasia

Cushing’s disease causes Cushing’s syndrome but is not always caused by it

Question 2

What are the causes of Cushing’s syndrome?

Answer 2

1. ACTH dependant causes
   - Cushing’s disease
   - Ecptopic (praneoplastic) ACTH production - small cell lung cancer most common cause
2. ACTH independant causes
   - iatrogenic: steroids
   - adrenal adenoma/ adrenal carcinoma
3. Pseudo-Cushing’s
   - mimics cushings
   - often due to alcohol excess or severe depression
   - causes false positive dexamethasone test or 24hr urinary free cortisol
   - insulin test may be used to differentiate

Question 3

What are the features of Cushing’s syndrome

Answer 3

Round in the middle with thin limbs

• round moon face
• central obesity
• abdominal striae
• buffalo hump
• proximal limb muscle wasting

high levels of stress hormone causes

• hyperglycaemia (T2DM)
• insomnia
• depression
• hypertension
• cardiac hypertrophy

Extra effects

• osteoporosis
• easy bruising a poor skin healing

Question 4

What investigations would you do for Cushing’s?

Answer 4

Dexameathosone suppression test

• low dose 1mg
• high dose 8mg

24 hr urinary free cortisol - alternative diagnosis but does not indicate underlying case

FBC (raised white cells) and electrolytes (K+ may be low if aldosterone also secreted by adrenal adenoma)

MRI brain - pituitary adenoma

Chest CT - small cell lung cancer

Abdominal CT - adrenal tumours

Question 5

What is the dexamthesone suppresion test used for?

Answer 5

used to diagnose cushing’s syndrome

low does given first - if normal cushing’s syndrome can be excluded (dexamethasone given the night before should suppress normal morning spike)

if abnormal - high dose test given to identify underlying cause

Question 6

What is the interpretation of possible results with high dose dexamethsone test?

Answer 6

If cortisol and ACTH are both suppressed - suggest pituitary adenoma

If cortisol not suppressed but ACTH is suppressed, suggest adrenal adenoma

If neither Cortisol nor ACTH suppressed, suggest ectopic ACTH production i.e paraneoplastic tumour

Question 7

What are the investigation findings may be seen in cushing’s syndrome?

Answer 7

Hypokalaemic metabolic alkalosis

impaired glucose tolerance

Question 8

What is the management of Cushing’s ?

Answer 8

dependant on underlying cause

Trans-phenoidal removal of pituitary tumour
surgical removal of adrenal tumour
surgical removal of tumour producing ectopic ACTH

if surgical removal not possible - remove both adrenal glands and lifelong steroid hormones